| Institution: | 1. Laboratory of Synthetic Organic Chemistry, Department of Chemistry, University of Patras, 26504 Patras, Greece;2. Biochemistry, Biochemical Analysis & Matrix Pathobiology Research Group, Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patras, Greece;3. Foundation for Research and Technology-Hellas (FORTH)/Institute of Chemical Engineering Sciences (ICE-HT), Patras, Greece;4. Lund University, Department of Laboratory Medicine, Malmö University Hospital, Malmö, Sweden;5. Department of Biological Applications and Technology, University of Ioannina, Ioannina 45110, Greece;6. Laboratory of Theoretical Chemistry, Department of Chemistry, University of Patras, 26504 Patras, Greece;1. Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland;2. Jerzy Haber Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, Kraków, Poland;1. Department of Mechanical engineering, University of Sao Paulo, Av. Trabalhador Sao Carlense n° 100, 13560-590 Sao Carlos, SP, Brasil;2. Department of Mechanical Engineering and Civil Construction, Universitat de Girona, Av. Lluis Santaló s/n, 17071 Girona, Spain;3. Centro Renato Archer, SP, Brasil;1. Department of Bionanotechnology, Gachon University, San 65, Bokjeong-Dong, Sujeong-Gu, Seongnam-Si, Gyeonggi-Do 461-701, Republic of Korea;2. Graduate Gachon Medical Research Institute, Gil Medical Center, Inchon 405-760, Republic of Korea;1. Testing and Analysis Center, Hebei Normal University, Shijiazhuang 050024, PR China;2. College of Chemistry & Material Science, Hebei Normal University, Shijiazhuang 050024, PR China;3. College of Chemical Engineering & Material, Handan University, Hebei Key Laboratory of Heterocyclic Compounds, Handan 056005, PR China;4. College of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059, China |
| Abstract: | Two new diastereomeric lignan amides (4 and 5) serving as dimeric caffeic acid-l-DOPA hybrids were synthesized. The synthesis involved the FeCl3-mediated phenol oxidative coupling of methyl caffeate to afford trans-diester 1a as a mixture of enantiomers, protection of the catechol units, regioselective saponification, coupling with a suitably protected l-DOPA derivative, separation of the two diastereomers thus obtained by flash column chromatography and finally global chemoselective deprotection of the catechol units. The effect of hybrids 4 and 5 and related compounds on the proliferation of two breast cancer cell lines with different metastatic potential and estrogen receptor status (MDA-MB-231 and MCF-7) and of one epithelial lung cancer cell line, namely A-549, was evaluated for concentrations ranging from 1 to 256 μM and periods of treatment of 24, 48 and 72 h. Both hybrids showed interesting and almost equipotent antiproliferative activities (IC50 64–70 μM) for the MDA-MB-231 cell line after 24–48 h of treatment, but they were more selective and much more potent (IC50 4–16 μM) for the MCF-7 cells after 48 h of treatment. The highest activity for both hybrids and both breast cancer lines was observed after 72 h of treatment (IC50 1–2 μM), probably as the result of slow hydrolysis of their methyl ester functions. |
